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Now, That’s What I Call High-Yield: Immunology

Immunology. It’s amazing, and we certainly would not have made it this far without it. People devote entire careers and decades of research to understanding single immunologic proteins, and you have a few weeks to develop an understanding of the science as a whole, and its place in clinical medicine. Can it be done?

Of course.

There’s lots of high-yield immunology material that you should work to understand inside and out. Sadly, some important information is nothing more than numbers and letters that you either know or you don’t. You can figure out the answer to a Step 1 question is hematopoietic stem cells, but did you remember that these cells have a CD34 marker? More important than any cluster of differentiation (CD##) is an understanding of flow and process. What takes place to get me from getting a breakdown in skin integrity to the formation of pus around entry site? How does that tetanus shot confer immunity to the bacterial toxin in the future? These bigger picture ideas are where to focus your efforts. Build the foundation first, then fill in the cracks with the facts.

Role of the spleen (7)

The spleen! You can live with it, you can live without it. But that doesn’t make it extraneous and useless! It has a crucial role in getting rid of those pesky encapsulated SHiN organisms (Strep, H. influenza, Neisseria), and has important ties to sickle-cell disease (think autosplenectomy; hypertrophy → atrophy). There’s also a lot of overlap with hematology, and interesting blood smear findings in the absence of a spleen. Lastly, remember its embryologic role of hematopoiesis in the fetus.

Role of B & T cells (9)

B & T cell structure and function are fundamental pillars of immunity, alongside the innate immunity conferred by the other types of leukocytes. B cells will always be at the ready to produce the antibodies you need. Remember their differentiation into the immunoglobulin factories known as plasma cells. T cells will churn out cytokines to activate other immune cells, and they can also kill virus cells directly. The two-signal system for B- and T-cell activation is also quite important. Go out of your way to understand the complex relationship and interdependence that all of these immune cells have on one another (e.g., antigen-presenting cells activating T cells, Th cell-B cell interaction, and resultant cytokine-driven Ig class switching).

Immunoglobulin structure and isotypes (9)

Just about everything regarding immunoglobulins is important. Ratios of the different types can help with disease diagnosis and time course. They are responsible for keeping newborns healthy (IgG that crossed the placenta, IgA in breast milk), keeping sinonasal and GI mucosa clean (secretory IgA), anaphylaxis (IgE), opsonization (IgG), and complement activation (IgG and IgM). A good grasp on the different immunoglobulins is necessary for understanding immunodeficiencies, too. There are loads of clinical correlates that stem from immunoglobulins: hepatitis diagnosis, hypersensitivities, and multiple myeloma, just to name a few.

Complement Pathway (7.5)

Just when you thought NK cells, macrophages, neutrophils, B & T cells were enough, you were laden with the complement pathway, and its constituents C1 through C9. If you can’t memorize every protein’s place in the schema, at least remember that C3a and C5a are your main anaphylactoid reactants, C3b is responsible for opsonization, and that the higher set of numbers (C5-9) is responsible for the almighty membrane attack complex.

Cytokines (9)

“What do you think is causing *** to happen?” your attending asks on rounds. “Cytokines,” you respond. Everyone has a brief chuckle, and you are in fact correct. Cytokines are responsible for so much of what is happening in the body at any given time. A shame there are countless ones to memorize. My advice here is to compartmentalize them based on function. IL-1, IL-6 and TNF-α are your heavy hitters in sepsis. IL-2 (IL-Two) gives strength and power to T-cells. TGF-β and IL-10 keep the immune system in check, attenuating the immune response.

Hypersensitivities (10)

Hypersensitivities are the perfect marriage of cellular mechanics and disease phenotypes, making them truly testable favorites. There are dozens of diseases and reactions that are explained by hypersensitivities. The low-hanging fruit:

Type I = IgE = mast cell degranulation = histamine = anaphylaxis.

Type II = Antibodies attaching to cells causing interference/destruction. Anti-GBM disease, ITP, myasthenia gravis, and Graves disease are some of the prototypical diseases here.

Type III = immune complex (type III = 3 parts, antigen-antibody-complement). These complexes can deposit in kidneys (PSGN), joints (SLE, RA), and blood vessels (HSP).

Type IV = cell mediated (no antibodies involved, unlike I-III) = cellular destruction (GVHD) or cytokine release (PPD testing, contact dermatitis).

Immunodeficiencies (7)

If you have a firm handle on how the immune system works, then understanding deficiencies in certain facets of the system shouldn’t be too difficult. B cell disorders lead to problems with antibody production. X-linked agammaglobulinemia is most important among them. For T-cell disorders, DiGeorge syndrome (thymic aplasia) is the one to know. SCID is quite important, and represents a problem in both B- and T-cell lineages. CGD is also worth knowing, as it connects the respiratory burst function with a disease.

Rejection (7)

Here’s your high-yield tip for different forms of organ rejection. It’s all about time-course. If, in your question stem, the organ gets ischemic in the operative field immediately after reperfusion, it is hyperacute, a type II hypersensitivity (preformed antibodies against donor), usually an accidental ABO mismatch. If the organ goes down after weeks-months, it is T-cell mediated (Type IV hypersensitivity) attack of the donor organ. That’s why transplant recipients take immunosupression medications…to keep these T-cells at bay. Chronic rejection takes months to years, and is due to a slow fibrosis of vessels to the graft.

No one is immune to learning immunology. View it as a beautifully interconnected system. Draw it out on a big piece of paper. Do what it takes to see the forest for the trees. Then learn about every tree in the forest!